Post-Finasteride Syndrome represents a Post-Androgen Deprivation Syndrome following exposure to antiandrogenic endocrine disruptors and without specificity to finasteride. The common pharmacological interruption of steroid signaling and remarkably similar clinical endpoints may imply that a single mechanistic disease state occurs in predisposed consumers following the use of medications including dutasteride, isotretinoin and serotonergic antidepressants. The lasting and profound changes to physiological and neurological health are alarming and the permanence suggests that, in predisposed individuals, epigenetic reorganisation is possible in somatic cells and postmitotic neurons following significant interruption of androgen signaling. The past decade has seen broad appreciation that either excessive or insufficient androgen signaling can prove deleterious to cellular homeostasis and biologic function (Gibson et al., 2018). These mechanistic underpinnings trace back to the influential work of Charles Huggins in the mid-20th century (Huggins, 1965).
We hypothesise a clinically significant AR deregulation is an aberrant manifestation of a conserved mechanism of cellular adaptation to lowered levels of availability or potency of androgenic ligand or interruption of appropriate transactivation of androgen regulated genes. Potential mechanistic factors can be contextualised by the rapidly expanding understanding of the ability of the androgen receptor to affect the basic epigenetic machinery and the structure of chromatin in addition to its essential regulatory functions. Understanding the pathology may provide extremely valuable insight regarding an increasingly apparent androgen-mediated pleiotropy of relevance to a broad spectrum of disease states often associated with the ageing process. Scientific elucidation of predisposing genetic factors will aid in establishing urgent protections for the public. Regulatory level action is necessary and overdue. We ask the medical community to begin efforts towards education regarding this novel condition and to shoulder the clinical responsibility of accurate diagnosis and appropriate follow up of PFS patients.
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- Gibson, D. A., Saunders, P. T. K., & McEwan, I. J. (2018). Androgens and androgen receptor: Above and beyond. Molecular and Cellular Endocrinology, 1–3. https://doi.org/10.1016/j.mce.2018.02.013
- Huggins, C. (1965). Two principles in endocrine therapy of cancers: Hormone deprival and hormone interference. Cancer Research, 25(7), 1163–1167.